Geriatric patients exhibit a high incidence of toxic drug effects. This may be caused by decreases in hepatic drug-metabolizing enzymes. Information concerning te effect of aging on drug metabolism is needed for the recommendation of types and dosages of drugs suitable for use in the elderly. Biotransformation of drugs and foreign chemicals occurs via the microsomal electron transport system, which consists of cytochrome P-450, NADPH-cytochrome P-450 reductase, and phosphatidyl choline. The proposed research will investigate age-related alterations in this system, using liver microsomes prepared from young-adult, middle-aged and senescent rats (Fishcer 344, males). Decreases in drug-metabolism activities will be correlated with qualitative or quantitative changes in microsomal electron transport components. The effect of aging on an animal's ability to increase drug-metabolism reactions in response to environmental stimuli will be investigated also. Inducing agents (phenobarbital, beta-naphthoflavone and testosterone) will be administered to rats in each of the three age groups and their effects on the various parameters of drug metabolism will be determined.